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040 _aEG-GiCUC
_beng
_cEG-GiCUC
041 0 _aeng
049 _aDeposite
097 _aPh.D
099 _aCai01.08.01.Ph.D.2021.Ma.S
100 0 _aMahmoud Taha Abdelaziz Aboelfadl
245 1 0 _aSynthetic lethality of triple negative breast cancer through trgeted silencing by small interfering RNA /
_cMahmoud Taha Abdelaziz Aboelfadl ; Supervised Manal Fouad Ismail , Nancy Nabil Shahin , Amira M. Gamal Aldeen
246 1 5 _aالموت الاصطناعى لسرطان الثدى ثلاتى السلبية من خلال الاسكات الموجه باستخدام الحمض النووى الريبوزى المتداخل الصغير
260 _aCairo :
_bMahmoud Taha Abdelaziz Aboelfadl ,
_c2021
300 _a262 P . :
_bcharts facsmilies ;
_c25cm
502 _aThesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry
520 _aBackground: TNFRSF13B, TACI, is a member of the TNF receptor superfamily; it plays a key role in cancer cell proliferation and progression. Method: Influence of silencing of human cytokine receptors on cell viability was screened by Luminescent Cell Viability Assay, after transfection with the siRNA library to find the maximum cell death superhits in both triple- negative MDAMB- 231 and triple-positive MCF-7 breast cells. The mode of cell death was investigated by dual DNA fluorescence staining. The expression of mRNAs of TACI, BAFF, BAFF-R, and APRIL was explored by qPCR. Immunocytofluorescence analysis was used to evaluate changes in TACI, Bcl-2, TNFR2, cyclin-D2, and PCNA. NF-kB p65, cell cycle, and necrosis/apoptosis (late and early) were analyzed by flowcytometry. Results: TACI was the most potent cytotoxic superhit resulting from highthroughput screening of the siRNA library, in both types of cells. Our findings indicated that silencing TACI receptor in both types of breast cancer cells led to significant cell death, after different intervals from siRNA transfection. Cell death mediators (TNF-R2, Bcl-2, and NF-mB p65) were significantly decreased after TACI silencing. The key factors for cell division (cyclin-D2 and PCNA) were significantly increased in silenced cells of both types but the cell cycle was arrested before the completion of mitosis. Expression of BAFF, BAFF-R and APRIL mRNA in TACI-silenced cells showed significant upregulation in MDAMB- 231 cells, while only BAFF-R and APRIL showed significant downregulation in MCF-7 cellsConclusion: TACI silencing can be a new and promising therapeutic strategy for mesenchymal-stem like triple- negative breast cancer subtype
530 _aIssued also as CD
653 4 _aRNA
653 4 _aSynthetic lethality
653 4 _aTriple negative breast cancer
700 0 _aAmira M. Gamal Aldeen,
_eSupervising
700 0 _aManal Fouad Ismail ,
_eSupervising
700 0 _aNancy Nabil Shahin ,
_eSupervising
856 _uhttp://172.23.153.220/th.pdf
905 _aAmira
_eCataloger
905 _aNazla
_eRevisor
942 _2ddc
_cTH
999 _c80960
_d80960